The Herpes Simplex Virus Type 1 BgKL Variant, Unlike the BgOL Variant, Shows a Higher Association with Orolabial Infection than with Infections at Other Sites, Supporting the Variant-Dispersion-Replacement Hypothesis

The identification and geographic distribution of the herpes simplex virus type 1 (HSV-1) BglII restriction fragment length polymorphism (RFLP) variants named BgKL and BgOL in clinical isolates from orolabial and cutaneous sites were described in our previous reports, in which the dispersion and replacement of HSV-1 variants were proposed. The base substitution sites deduced from the BgKL multiple RFLP variations were mapped to the UL12 (DNase), RL2 (α0 transactivator), and latency-associated transcript genes in the present study. The results show that the relative frequencies (RFs) of BgKL are significantly higher in orolabial and cutaneous HSV-1 infections than in ocular infections. For the BgOL variant, the opposite was found; i.e., the RF of BgOL was significantly lower in orolabial and cutaneous infections than in ocular infections. No significant differences in the RFs of non-BgKL:non-BgOL isolates were observed. The ratio of the BgKL RF to the BgOL RF was much higher for the orolabial and cutaneous infection groups than for the ocular infection group, whereas the BgKL RF-to-non-BgKL:non-BgOL RF ratios for the former groups were slightly higher than those for the latter group. The higher efficiency of orolabial and cutaneous infections caused by BgKL compared to the efficiency of infections caused by BgOL allows BgKL to spread more efficiently in human populations and to displace BgOL, because the mouth and lips are the most common HSV-1 infection sites in children. The present study supports our HSV-1 dispersion-and-replacement hypothesis and suggests that HSV-1, the latency-reactivation of which allows variants to accumulate in human populations, has evolved under competitive conditions, providing a new perspective on the polymorphism or variation of HSV-1.